Drug Delivery and Translational Research最新文献_第8页

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery. 提高鱼腥草素的口服生物利用度：基于多糖的自纳米乳化球体用于结肠靶向给药。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-05-24 DOI: 10.1007/s13346-024-01634-6

Pradnya Gunjal, Sukriti Vishwas, Rajan Kumar, Bushra Bashir, Bimlesh Kumar, Navneet Khurana, Monica Gulati, Gaurav Gupta, Parteek Prasher, Popat Kumbhar, John Disouza, Gowthamarajan Kuppusamy, Yousuf Mohammed, Harish Dureja, Kamal Dua, Sachin Kumar Singh

{"title":"Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.","authors":"Pradnya Gunjal, Sukriti Vishwas, Rajan Kumar, Bushra Bashir, Bimlesh Kumar, Navneet Khurana, Monica Gulati, Gaurav Gupta, Parteek Prasher, Popat Kumbhar, John Disouza, Gowthamarajan Kuppusamy, Yousuf Mohammed, Harish Dureja, Kamal Dua, Sachin Kumar Singh","doi":"10.1007/s13346-024-01634-6","DOIUrl":"10.1007/s13346-024-01634-6","url":null,"abstract":"Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1-17"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunostimulatory nanoparticles delivering cytokines as a novel cancer nanoadjuvant to empower glioblastoma immunotherapy. 提供细胞因子的免疫刺激纳米粒子是一种新型癌症纳米辅助剂，可增强胶质母细胞瘤的免疫疗法。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2023-12-31 DOI: 10.1007/s13346-023-01509-2

Flávia Sousa, Henry Lee, Mauro Almeida, Amelie Bazzoni, Barbara Rothen-Rutishauser, Alke Petri-Fink

{"title":"Immunostimulatory nanoparticles delivering cytokines as a novel cancer nanoadjuvant to empower glioblastoma immunotherapy.","authors":"Flávia Sousa, Henry Lee, Mauro Almeida, Amelie Bazzoni, Barbara Rothen-Rutishauser, Alke Petri-Fink","doi":"10.1007/s13346-023-01509-2","DOIUrl":"10.1007/s13346-023-01509-2","url":null,"abstract":"Glioblastoma (GBM) stands as a highly aggressive and deadly malignant primary brain tumor with a median survival time of under 15 months upon disease diagnosis. While immunotherapies have shown promising results in solid cancers, brain cancers are still unresponsive to immunotherapy due to immunological dysfunction and the presence of a blood-brain barrier. Interleukin-12 (IL-12) emerges as a potent cytokine in fostering anti-tumor immunity by triggering interferon-gamma production in T and natural killer cells and changing macrophages to a tumoricidal phenotype. However, systemic administration of IL-12 toxicity in clinical trials often leads to significant toxicity, posing a critical hurdle. To overcome this major drawback, we have formulated a novel nanoadjuvant composed of immunostimulatory nanoparticles (ISN) loaded with IL-12 to decrease IL-12 toxicity and enhance the immune response by macrophages and GBM cancer cells. Our in vitro results reveal that ISN substantially increase the production of pro-inflammatory cytokines in GBM cancer cells (e.g. 2.6 × increase in IL-8 expression compared to free IL-12) and macrophages (e.g. 2 × increase in TNF-α expression and 6 × increase in IL-6 expression compared to the free IL-12). These findings suggest a potential modulation of the tumor microenvironment. Additionally, our study demonstrates the effective intracellular delivery of IL-12 by ISN, triggering alterations in the levels of pro-inflammatory cytokines at both transcriptional and protein expression levels. These results highlight the promise of the nanoadjuvant as a prospective platform for resharing the GBM microenvironment and empowering immunotherapy.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2655-2667"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OX26-cojugated gangliosilated liposomes to improve the post-ischemic therapeutic effect of CDP-choline. OX26 共轭神经节硅脂质体改善 CDP-choline 的缺血后治疗效果。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-03-13 DOI: 10.1007/s13346-024-01556-3

Nicola d'Avanzo, Donatella Paolino, Antonella Barone, Luigi Ciriolo, Antonia Mancuso, Maria Chiara Christiano, Anna Maria Tolomeo, Christian Celia, Xiaoyong Deng, Massimo Fresta

{"title":"OX26-cojugated gangliosilated liposomes to improve the post-ischemic therapeutic effect of CDP-choline.","authors":"Nicola d'Avanzo, Donatella Paolino, Antonella Barone, Luigi Ciriolo, Antonia Mancuso, Maria Chiara Christiano, Anna Maria Tolomeo, Christian Celia, Xiaoyong Deng, Massimo Fresta","doi":"10.1007/s13346-024-01556-3","DOIUrl":"10.1007/s13346-024-01556-3","url":null,"abstract":"Cerebrovascular impairment represents one of the main causes of death worldwide with a mortality rate of 5.5 million per year. The disability of 50% of surviving patients has high social impacts and costs in long period treatment for national healthcare systems. For these reasons, the efficacious clinical treatment of patients, with brain ischemic stroke, remains a medical need. To this aim, a liposome nanomedicine, with monosialic ganglioside type 1 (GM1), OX26 (an anti-transferrin receptor antibody), and CDP-choline (a neurotrophic drug) (CDP-choline/OX26Lip) was prepared. CDP-choline/OX26Lip were prepared by a freeze and thaw method and then extruded through polycarbonate filters, to have narrow size distributed liposomes of ~80 nm. CDP-choline/OX26Lip were stable in human serum, they had suitable pharmacokinetic properties, and 30.0 ± 4.2% of the injected drug was still present in the blood stream 12 h after its systemic injection. The post-ischemic therapeutic effect of CDP-choline/OX26Lip is higher than CDP-choline/Lip, thus showing a significantly high survival rate of the re-perfused post-ischemic rats, i.e. 96% and 78% after 8 days. The treatment with CDP-choline/OX26Lip significantly decreased the peroxidation rate of ~5-times compared to CDP-choline/Lip; and the resulting conjugated dienes, that was 13.9 ± 1.1 mmol/mg proteins for CDP-choline/Lip and 3.1 ± 0.8 for CDP-choline/OX26Lip. OX26 increased the accumulation of GM1-liposomes in the brain tissues and thus the efficacious of CDP-choline. Therefore, this nanomedicine may represent a strategy for the reassessment of CDP-choline to treat post-ischemic events caused by brain stroke, and respond to a significant clinical need.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2771-2787"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tunable polymeric micelles for taxane and corticosteroid co-delivery. 紫杉烷和皮质类固醇共递送的可调聚合胶束。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2023-11-14 DOI: 10.1007/s13346-023-01465-x

Armin Azadkhah Shalmani, Alec Wang, Zaheer Ahmed, Maryam Sheybanifard, Rahaf Mihyar, Eva Miriam Buhl, Michael Pohl, Wim E Hennink, Fabian Kiessling, Josbert M Metselaar, Yang Shi, Twan Lammers, Quim Peña

{"title":"Tunable polymeric micelles for taxane and corticosteroid co-delivery.","authors":"Armin Azadkhah Shalmani, Alec Wang, Zaheer Ahmed, Maryam Sheybanifard, Rahaf Mihyar, Eva Miriam Buhl, Michael Pohl, Wim E Hennink, Fabian Kiessling, Josbert M Metselaar, Yang Shi, Twan Lammers, Quim Peña","doi":"10.1007/s13346-023-01465-x","DOIUrl":"10.1007/s13346-023-01465-x","url":null,"abstract":"Nanomedicine holds promise for potentiating drug combination therapies. Increasing (pre)clinical evidence is available exemplifying the value of co-formulating and co-delivering different drugs in modular nanocarriers. Taxanes like paclitaxel (PTX) are widely used anticancer agents, and commonly combined with corticosteroids like dexamethasone (DEX), which besides for suppressing inflammation and infusion reactions, are increasingly explored for modulating the tumor microenvironment towards enhanced nano-chemotherapy delivery and efficacy. We here set out to develop a size- and release rate-tunable polymeric micelle platform for co-delivery of taxanes and corticosteroids. We synthesized amphiphilic mPEG-b-p(HPMAm-Bz) block copolymers of various molecular weights and used them to prepare PTX and DEX single- and double-loaded micelles of different sizes. Both drugs could be efficiently co-encapsulated, and systematic comparison between single- and co-loaded formulations demonstrated comparable physicochemical properties, encapsulation efficiencies, and release profiles. Larger micelles showed slower drug release, and DEX release was always faster than PTX. The versatility of the platform was exemplified by co-encapsulating two additional taxane-corticosteroid combinations, demonstrating that drug hydrophobicity and molecular weight are key properties that strongly contribute to drug retention in micelles. Altogether, our work shows that mPEG-b-p(HPMAm-Bz) polymeric micelles serve as a tunable and versatile nanoparticle platform for controlled co-delivery of taxanes and corticosteroids, thereby paving the way for using these micelles as a modular carrier for multidrug nanomedicine.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2642-2654"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding the role of the structure of single-stimuli hybrid systems on their behaviour as platforms for colonic delivery. 了解单刺激混合系统的结构对其作为结肠输送平台的作用。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-06-10 DOI: 10.1007/s13346-024-01641-7

Joaquín González-Fuentes, María Plaza-Oliver, Manuel Jesús Santander-Ortega, María Victoria Lozano

{"title":"Understanding the role of the structure of single-stimuli hybrid systems on their behaviour as platforms for colonic delivery.","authors":"Joaquín González-Fuentes, María Plaza-Oliver, Manuel Jesús Santander-Ortega, María Victoria Lozano","doi":"10.1007/s13346-024-01641-7","DOIUrl":"10.1007/s13346-024-01641-7","url":null,"abstract":"The success of colon-targeted oral hybrid systems relies in the proper control over the release of the entrapped nanostructures at the colon. This work describes the design of hybrid systems for their colonic enzyme-triggered release. The hybrid systems were constituted by nanoemulsions, with adequate characteristics for the treatment of ulcerative colitis, included in a pectin hydrogel-like matrix. For that purpose, pectins with similar degrees of methylation (< 50%) and increasing degree of amidation, i.e. 0, 13 and 20%, were selected. Hybrid systems were formulated by a novel aggregation induced gelation method, using Ca2+, Ba2+ or Zn2+ as aggregating agents, as well as by a polyelectrolyte condensation approach, obtaining structures in the micrometric range (< 10 μm). Despite the resistance of pectins to the upper gastrointestinal tract stimuli, the analysis of the behaviour of the different prototypes showed that the non-covalent crosslinks that allow the formation of the hybrid structure may play a relevant role on the performance of the formulation.Our results indicated that the partial disassembling of the hybrid system's microstructure due to the intestinal conditions may facilitate the stimuli-triggered release of the nanoemulsions at the colon. More interestingly, the particle tracking experiments showed that the condensation process that occurs during the formation of the system may affect to the enzymatic degradation of pectin. In this sense, the effect of the high degree of amidation of pectin may be more prevalent as structural feature rather than as a promoter of the enzyme-triggered release.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2598-2614"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RGD-coated polymeric microbubbles promote ultrasound-mediated drug delivery in an inflamed endothelium-pericyte co-culture model of the blood-brain barrier. 在血脑屏障的炎性内皮-冰细胞共培养模型中，RGD 涂层聚合物微气泡可促进超声介导的药物输送。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-03-18 DOI: 10.1007/s13346-024-01561-6

Christopher Hark, Junlin Chen, Julia Blöck, Eva Miriam Buhl, Harald Radermacher, Robert Pola, Michal Pechar, Tomáš Etrych, Quim Peña, Anne Rix, Natascha I Drude, Fabian Kiessling, Twan Lammers, Jan-Niklas May

{"title":"RGD-coated polymeric microbubbles promote ultrasound-mediated drug delivery in an inflamed endothelium-pericyte co-culture model of the blood-brain barrier.","authors":"Christopher Hark, Junlin Chen, Julia Blöck, Eva Miriam Buhl, Harald Radermacher, Robert Pola, Michal Pechar, Tomáš Etrych, Quim Peña, Anne Rix, Natascha I Drude, Fabian Kiessling, Twan Lammers, Jan-Niklas May","doi":"10.1007/s13346-024-01561-6","DOIUrl":"10.1007/s13346-024-01561-6","url":null,"abstract":"Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2629-2641"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycyrrhizin functionalized CuS Nanoprobes for NIR Light-based therapeutic mitigation of acne vulgaris. 甘草酸苷功能化 CuS 纳米探针用于基于近红外光的痤疮治疗缓解。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-05-04 DOI: 10.1007/s13346-024-01594-x

Srivathsan Ganeshan, Nidhi Parihar, Donker Chonzom, Dinesh Mohanakrishnan, Rajdeep Das, Dandadhar Sarma, Devipriya Gogoi, Manash Ranjan Das, Suryanarayana Murty Upadhayula, Deepak Bharadwaj Pemmaraju

{"title":"Glycyrrhizin functionalized CuS Nanoprobes for NIR Light-based therapeutic mitigation of acne vulgaris.","authors":"Srivathsan Ganeshan, Nidhi Parihar, Donker Chonzom, Dinesh Mohanakrishnan, Rajdeep Das, Dandadhar Sarma, Devipriya Gogoi, Manash Ranjan Das, Suryanarayana Murty Upadhayula, Deepak Bharadwaj Pemmaraju","doi":"10.1007/s13346-024-01594-x","DOIUrl":"10.1007/s13346-024-01594-x","url":null,"abstract":"Acne Vulgaris or Acne is a multifactorial bacterial infection caused by Propionibacterium acne, leading to inflammation and decreased quality of life, especially in adolescence. Currently, antibiotics and retinoids are preferred for treating acne. However, their continuous usage may lead to anti-microbial resistance and other side effects. Therefore, research on developing effective strategies to reduce antimicrobial resistance and improve acne healing is ongoing. The current work reports the synthesis and evaluation of near-infrared light-absorbing copper sulfide (CuS) nanoparticles loaded with a biomolecule, Glycyrrhizin (Ga). The photothermal efficacy studies, and in-vitro and in-vivo experiments indicated that the Ga-CuS NPs generated localized hyperthermia in acne-causing bacteria, leading to their complete growth inhibition. The results indicated that the Ga-Cus NPs possess excellent antibacterial and anti-inflammatory properties in the acne and inflammatory models. This could be from the synergistic effect of CuS NPs mediated mild Photothermal effect and inherent pharmacological properties of Ga. Further detailed studies of the formulations can pave the way for application in cosmetic clinics for the effective and minimally invasive management of Acne-like conditions.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2727-2742"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid nanoparticles-based RNA therapies for breast cancer treatment. 用于治疗乳腺癌的基于脂质纳米粒子的 RNA 疗法。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-06-03 DOI: 10.1007/s13346-024-01638-2

Luigia Serpico, Yuewen Zhu, Renata Faria Maia, Sumedha Sumedha, Mohammad-Ali Shahbazi, Hélder A Santos

{"title":"Lipid nanoparticles-based RNA therapies for breast cancer treatment.","authors":"Luigia Serpico, Yuewen Zhu, Renata Faria Maia, Sumedha Sumedha, Mohammad-Ali Shahbazi, Hélder A Santos","doi":"10.1007/s13346-024-01638-2","DOIUrl":"10.1007/s13346-024-01638-2","url":null,"abstract":"Breast cancer (BC) prevails as a major burden on global healthcare, being the most prevalent form of cancer among women. BC is a complex and heterogeneous disease, and current therapies, such as chemotherapy and radiotherapy, frequently fall short in providing effective solutions. These treatments fail to mitigate the risk of cancer recurrence and cause severe side effects that, in turn, compromise therapeutic responses in patients. Over the last decade, several strategies have been proposed to overcome these limitations. Among them, RNA-based technologies have demonstrated their potential across various clinical applications, notably in cancer therapy. However, RNA therapies are still limited by a series of critical issues like off-target effect and poor stability in circulation. Thus, novel approaches have been investigated to improve the targeting and bioavailability of RNA-based formulations to achieve an appropriate therapeutic outcome. Lipid nanoparticles (LNPs) have been largely proven to be an advantageous carrier for nucleic acids and RNA. This perspective explores the most recent advances on RNA-based technology with an emphasis on LNPs' utilization as effective nanocarriers in BC therapy and most recent progresses in their clinical applications.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2823-2844"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye. 对纳米治疗玻璃体替代物进行体内评估，以将曲安奈德精确输送到眼球后段。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-03-22 DOI: 10.1007/s13346-024-01566-1

Kruti Naik, Lisa Claire du Toit, Naseer Ally, Yahya Essop Choonara

{"title":"In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye.","authors":"Kruti Naik, Lisa Claire du Toit, Naseer Ally, Yahya Essop Choonara","doi":"10.1007/s13346-024-01566-1","DOIUrl":"10.1007/s13346-024-01566-1","url":null,"abstract":"This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2668-2694"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of antigen loading in tolerogenic nanoparticles to mitigate Th2-mediated allergic lung inflammation. 耐受性纳米粒子中的抗原负载对减轻 Th2 介导的过敏性肺部炎症的影响。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-06-11 DOI: 10.1007/s13346-024-01632-8

Brianna L Scotland, Shruti Dharmaraj, Andrea L Cottingham, Nhu Truong, Svetlana P Chapoval, Achsah D Keegan, Ryan M Pearson

{"title":"Impact of antigen loading in tolerogenic nanoparticles to mitigate Th2-mediated allergic lung inflammation.","authors":"Brianna L Scotland, Shruti Dharmaraj, Andrea L Cottingham, Nhu Truong, Svetlana P Chapoval, Achsah D Keegan, Ryan M Pearson","doi":"10.1007/s13346-024-01632-8","DOIUrl":"10.1007/s13346-024-01632-8","url":null,"abstract":"Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2930-2944"},"PeriodicalIF":5.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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